Insect antifeedants synthesis

The key step in the diastereoselective synthesis of model insect antifeedant 152 starting from a-cyclocitral 148 was the INOC reaction of oxime 149 or nitro alkane 150 to the isoxazoline 151 (Eq. 15) [42]. 

A diastereoselective synthesis of the model insect antifeedant related to 12-hydroxyazadi-radione starting from a-cyclocitral has been reported. [The key steps involve INOC and a Stille... 

Sesquiterpenoids possessing the drimane skeleton (22) exhibit an impressive series of biological properties. Recently, all aspects relative to occurrence [76], biological activity [76], insect antifeedant properties [77] and synthesis [78] of these terpenoids have been exhaustively reviewed. 

Ginkgolide A (diterpenoid) Ginkgo biloba (maidenhair tree) (Ginkgoaceae) [root bark, leaf] [Reduces expression of adrenocortical mitochondrial PBZ-R thence corticosteroid synthesis AI, anti-asthmatic, antistress, insect antifeedant, bitter, neuroprotective]... 

The third and final general protocol for the hydrolysis of 5 5-acetals exploits the very easy reaction of the sulfur atom of an S-acetal with alkylating agents such as iodomethane, trimethyl- or triethyl-oxonium tetrafluoroborate, and methyl triHuoromethanesuLfonate to form the corresponding trialkylsulfonium salts. Ley s approach to the potent insect antifeedant Azadirachtin [Scheme 2 81]135,171,172 benefited from an easy S-alkylation-hydrolysis sequence. In a synthesis of Epiantillatoxin, a more difficult liberation of an aldehyde from its dithiane derivative was accomplished without rearrangement of a p,y-alkene into conjugation [Scheme 2,82].173... 

The potent biological activity (insect antifeedant, antitumour, antifungal) of warburganal (35) has stimulated considerable synthetic interest in this compound. Three total syntheses of this compound have been recorded in the period under review. " The synthesis by Tanis and Nakanishi has additional flexibility since the key intermediate diol (34) can be used in the syntheses of cinnamolide (36), drimenin (37), and polygodial (38). Both norisoambreinolide (39 R = O) and isoambrox (39 R = H2) have been synthesized from (40), the product of the stannic chloride-catalysed cyclization of farnesyl phenyl sulphone. Yahazunol (41), a bicyclofarnesyl hydroquinone, has been identified in the brown seaweed... 

K. Mori and H. Watanabe, Synthesis of both the enantiomers of polygodial, an insect antifeedant sesquiterpene. Tetrahedron, 42 (1986) 273-281. 

The diverse biological activity (e.g. insect antifeeding, plant growth regulation, molluscicidal) of a number of drimane sesquiterpenoids has stimulated considerable interest in their synthesis and the year under review has seen many new developments and improvements. Much of the synthetic work has centred around the key bicyclic diester (54) derived from 1-vinyl-2,6,6-trimethylcyclohexene and dimethyl acetylenedicarboxylate. In contrast to earlier results,34 Ley et al.8S... 

This approach was then extended to the synthesis of structure 480 (Scheme 45), a compound believed to represent the structure of specionin, an insect antifeedant isolated from the leaves of Catalpa speciosa, Warder. It turned out that 480 was not identical to specionin, and after correctly predicting the structure 481," they went on to synthesize it (Scheme 45). °... 

The transformation of a series of norbomanone derivatives (Fig. 16.5-34) was studied by Roberts and coworkers who determined that both the MOl complement of NADH dependent BVMOs from Pseudomonas putida ATCC 17453 and the NADPH dependent fraction M02 were successful in the resolution of hydroxy, acetoxy and benzyloxy norbomanones11231. Interestingly 25DKCMO and 36DKCMO when separate, displayed notably different reactivity toward the hydroxy and acetoxy derivative, again emphasizing their complementary nature as potential individual biocatalysts. The benzyloxy lactone is an intermediate in the synthesis of the insect antifeedant azadirachtin. 

A nice example of the foregoing stratagem is seen in equation (17) enone (6) undergoes copper(I)-catalyzed reaction with vinylmagnesium bromide from its less-hindered face to give an enolate that reacts with formaldehyde from the opposite face to provide decalone (7), an intermediate in the synthesis of insect antifeedants. Yoshida and coworkers have used this method for the stereospecific generation of tetrasubstituted thioamide enolates, which undergo remarkably stereoselective aldol reactions (equation 18). ° The stereochemistry of this process is discussed in Section 1.6.3.6. 

In a previous paper [1], we reviewed the isolation of quassinoids, alkaloids, and fatty acids from Simaroubaceous plants during the period 1972-1988 and discussed their biological activities, such as antitumor, antimalarial, and anti-inflammatory agents as well as insect antifeedants, amoebicides, and herbicides. This review will add new quassinoids isolated from Simaroubaceous plants from 1988 onwards and their biological activities, for example, antitumor, anti-tumor-promotor (= inhibitor against TPA-induced EBV-EA activation), anti-HIV, anti-tuberculosis, and insect antifeedant activities. Furthermore, the stability of quassinoids, lower activities of degradation products, and the synthesis of fluorinated quassinoids are also described. 

Paquette, L.A., Hu, Y, Luxenburger, A. and Bishop, R.L. (2007) Studies toward the total synthesis of dumsin. 2. A second generation approach resulting in enantioselective construction of a functionalized ABC subunit of the tetranortriterpenoid insect antifeedant. The Journal of Organic Chemistry, 72, 209-222. 

A number of these compounds have insect antifeedant activity. The total synthesis of the substituted c/s-decalin (26) as an antifeedant has been reported. Clerodanes have previously been detected in Salvia (Labiatae) species. The gesnerohlins A and B, obtained from S. gesneraefolia, have been assigned the structures (27) and (28) although their absolute stereochemistry was not determined. A further series of clerodanes of uncertain stereochemistry has been isolated from Baccharis species, including bacrispine (29) from B. crispa and the malonate ester (30) from B. tricuneata. ... 

Their biosynthesis proceeds through geranylgeranyl diphosphate, cyclization and rearrangement of the resulting labdadienyl cation. Antibiotic, antitumor, and insect antifeedant properties have been described. IM. J. Indian Chem. Soc. 75, 552 (1998) (isolation) Nat Prod. Rep. 9, 243 - 287 (1992) Synlett 1998,912 (synthesis) Tetrahedron 44, 6607-6622 (1988) Zechmeister 63, 107-196. 

Intramolecular 1,3-dipolar cycloaddition has been employed for the synthesis of various natural products as well. For instance, Mateos et al. reported a diastereoselective synthesis of the model insect antifeedant 281 related to 12-hydroxyazadiradione utihzing the intramolecular nitrile oxide cycloaddition (Scheme 65) [167]. The nitro compound 279 was synthesized from a-cyclocitral 278 in four steps. The cleavage of isoxazoline 280 was performed under three different conditions Raney Ni-mediated cleavage in methanol-water-acetic acid provided the epimeric ketoalcohol 282 in 5 3 ratio. While there was 100% selectivity in favor of the axial alcohol 282a in the presence of Pd/C and boric acid, the selectivity was in favor of the equatorial alcohol 282b when boric acid was replaced by acetic acid. 

Ley, S. V., D. Santafianos, W. M. Blaney, and M. S. J. Sim-monds. Synthesis of a hydroxy dihydrofuran acetal related to azadirachtin A potent insect antifeedant. Tetrahedron Lett., 28, 221-224 (1987). 

B. J. M. Jansen, Total Synthesis of Insect Antifeedant Drimane Sesquiterpenes, Ph.D. Thesis, University of Wageningen, 1997. 

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